ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.851G>T (p.Gly284Val) (rs119455957)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531153 SCV000628919 pathogenic Neuronal ceroid lipofuscinosis 2020-01-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 284 of the TPP1 protein (p.Gly284Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the homozygous or compound heterozygous state in many individuals affected with late-infantile neuronal ceroid lipofuscinosis (CLN2) (PMID: 18684116, 12414822, 11339651). ClinVar contains an entry for this variant (Variation ID: 2647). Experimental studies have shown that this missense change effects the function and structure of the TPP1 protein (PMID: 20340139, 19038966). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763266 SCV000893909 pathogenic Ceroid lipofuscinosis neuronal 2; Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia 2018-10-31 criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000002766 SCV001193869 pathogenic Ceroid lipofuscinosis neuronal 2 2019-11-11 criteria provided, single submitter clinical testing NM_000391.3(TPP1):c.851G>T(G284V) is classified as pathogenic in the context of TPP1-related neuronal ceroid lipofuscinosis and is associated with the late-infantile form of this disease. Sources cited for classification include the following: PMID 18684116, 12414822, 11339651 and 20340139. Classification of NM_000391.3(TPP1):c.851G>T(G284V) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000002766 SCV000022924 pathogenic Ceroid lipofuscinosis neuronal 2 2008-09-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000002766 SCV000091200 not provided Ceroid lipofuscinosis neuronal 2 no assertion provided not provided

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